American journal of respiratory and critical care medicine最新文献

{"title":"Reply to Rui and Chen: Initial Success: Camlipixant in Refractory Chronic Cough.","authors":"Jaclyn A Smith","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial Success: Camlipixant in Refractory Chronic Cough.","authors":"Yang Rui, Zhe Chen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficient FANCL Predisposes Endothelial Damage: A New Therapeutic Target for Pulmonary Hypertension.","authors":"Shiyun Liu, Xiaoqian Shan, Yufei Sun, Haixia Chen, Huazhuo Feng, Shaocong Mo, Changlei Bao, Junqi Zhu, Zizhou Zhang, Feng Wei, Xiuzhen Bai, Ran Xu, Jiaxuan Lai, Haiyun Luo, Chenting Zhang, Xiaoyun Luo, Qian Jiang, Yuqin Chen, Yuqi Zhou, Haiyang Tang, Lei Xu, Wenju Lu, Rong Guo, Chunli Liu, Zifeng Yang, Jason X-J Yuan, Xinlin Xu, Dongyi Xu, Jian Wang, Kai Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>Clinical observations have suggested an association between alkylating agents-based chemotherapy and pulmonary arterial hypertension (PAH). The Fanconi anemia (FA) pathway, principal mechanism for resolving alkylating agent-induced DNA damage, has been implicated in this process.</p><p><strong>Objectives: </strong>To establish the interplay among FA pathway, DNA damage and PAH.</p><p><strong>Methods: </strong>A knockout-first mouse model for FA complementation group L (<i>Fancl</i>^kf/kf) and an adeno-associated virus 9-mediated <i>Fancl</i> overexpression (AAV-<i>Fancl</i>) model were used. Lung specimens, pulmonary arterial endothelial cells (PAECs) from patients with PAH, and primarily cultured pulmonary microvascular endothelial cells (PMVECs) from wild-type and <i>Fancl</i>^kf/kf mice were analyzed.</p><p><strong>Measurements and main results: </strong>Data analysis on lung single-cell RNA sequencing datasets revealed significant downregulation of <i>FANCL</i> in endothelial cells from idiopathic PAH (IPAH) patients, a finding consistently validated in both clinical samples (lung specimens and PAECs) and the monocrotaline-induced PAH rat model. Notably, <i>Fancl</i>^kf/kf mice developed spontaneous PAH and showed heightened susceptibility to alkylating agent (mitomycin C)-induced PAH, characterized by severe DNA damage and apoptosis in PMVECs. These pathological phenotypes were rescued through <i>Fancl</i> gene supplementation via AAV-<i>Fancl</i> or pharmacological intervention with the DNA damage protector amifostine. Mechanistically, transcriptomic profiling combined with functional validation demonstrated a suppressed bone morphogenetic protein (BMP) signaling coupled with hyperactivated transforming growth factor beta (TGF-β) pathways in PMVECs from <i>Fancl</i>^kf/kf mice. Importantly, this imbalance was fully restored in PMVECs from AAV-<i>Fancl</i>-treated mice.</p><p><strong>Conclusions: </strong>Deficient <i>Fancl</i> plays a key role to promote PAH and targeted rescue of <i>Fancl</i> could be a novel effective strategy for the treatment of PAH.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant Form of <i>SFTPB</i>: A New Paradigm.","authors":"Camille Louvrier, Bruno Crestani, Raphaël Borie","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper Airway Volume Predicts Brain Structure and Cognition in Adolescents.","authors":"Adway Kanhere, Nithya Navarathna, Paul H Yi, Vishwa S Parekh, Jerrah Pickle, Christine C Cloak, Thomas Ernst, Linda Chang, Dongdong Li, Susan Redline, Amal Isaiah","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>One in ten children experiences sleep-disordered breathing (SDB). Untreated SDB is associated with poor cognition, but the underlying mechanisms are less understood.</p><p><strong>Objective: </strong>We assessed the relationship between magnetic resonance imaging (MRI)-derived upper airway volume and children's cognition and regional cortical gray matter volumes.</p><p><strong>Methods: </strong>We used five-year data from the Adolescent Brain Cognitive Development study (n=11,875 children, 9-10 years at baseline). Upper airway volumes were derived using a deep learning model applied to 5,552,640 brain MRI slices. The primary outcome was the Total Cognition Composite score from the National Institutes of Health Toolbox (NIH-TB). Secondary outcomes included other NIH-TB measures and cortical gray matter volumes.</p><p><strong>Results: </strong>The habitual snoring group had significantly smaller airway volumes than non-snorers (mean difference=1.2 cm³; 95% CI, 1.0-1.4 cm³; P<0.001). Deep learning-derived airway volume predicted the Total Cognition Composite score (estimated mean difference=3.68 points; 95% CI, 2.41-4.96; P<0.001) per one-unit increase in the natural log of airway volume (~2.7-fold raw volume increase). This airway volume increase was also associated with an average 0.02 cm³ increase in right temporal pole volume (95% CI, 0.01-0.02 cm³; P<0.001). Similar airway volume predicted most NIH-TB domain scores and multiple frontal and temporal gray matter volumes. These brain volumes mediated the relationship between airway volume and cognition.</p><p><strong>Conclusions: </strong>We demonstrate a novel application of deep learning-based airway segmentation in a large pediatric cohort. Upper airway volume is a potential biomarker for cognitive outcomes in pediatric SDB, offers insights into neurobiological mechanisms, and informs future studies on risk stratification. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robotic versus Electromagnetic Bronchoscopy for Peripheral Pulmonary Lesions: A Randomized Trial (RELIANT).","authors":"Rafael Paez, Robert J Lentz, Jennifer D Duke, Justin K Siemann, Cristina Salmon, Greta J Dahlberg, Ankush Ratwani, Jonathan D Casey, Heidi Chen, Sheau-Chiann Chen, Samira Shojaee, Otis B Rickman, Cheryl L Gatto, Todd W Rice, Fabien Maldonado","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>Robotic assisted bronchoscopy has emerged as an alternative to electromagnetic navigational bronchoscopy for patients undergoing bronchoscopic biopsy of a peripheral pulmonary lesion. While both platforms are routinely used in clinical practice, comparative effectiveness data are lacking.</p><p><strong>Objective: </strong>To compare the effectiveness of robotic assisted and electromagnetic navigational bronchoscopy for evaluation of peripheral pulmonary lesions.</p><p><strong>Methods: </strong>In an investigator-initiated, single-center, cluster randomized noninferiority trial, we assigned patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion to either robotic assisted or electromagnetic navigational bronchoscopy. The cluster randomization unit was the operating room in which patients were scheduled. The primary outcome was the diagnostic yield of the procedure, defined as the proportion of cases yielding lesional tissue. Secondary and safety outcomes included procedure duration and complications.</p><p><strong>Measurements and main results: </strong>Among the 411 patients included in the modified intention to treat analysis, lesional tissue was obtained in 158 of 203 (77.8%) patients in the robotic assisted group and 157 of 208 (75.5%) patients in the electromagnetic group, p-value for non-inferiority 0.007. The median duration of bronchoscopy was 37 minutes in the robotic assisted group and 32 minutes in the electromagnetic group (difference, 5 minutes; 95% confidence interval 2.0 to 7.7). Pneumothorax occurred in 4 patients in the robotic assisted group and 6 patients in the electromagnetic group.</p><p><strong>Conclusions: </strong>In patients undergoing bronchoscopy for the evaluation of a peripheral pulmonary lesion, the diagnostic yield of robotic assisted bronchoscopy was not inferior to that of electromagnetic navigation bronchoscopy. Clinical trial registration available at www.</p><p><strong>Clinicaltrials: </strong>gov, ID: NCT05705544. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucus Plug Density and Type 2 Inflammation in Asthma and/or COPD: Ultra-High-Resolution CT Study.","authors":"Naoya Tanabe, Hisako Matsumoto, Yusuke Hayashi, Ryo Sakamoto, Hironobu Sunadome, Susumu Sato, Atsuyasu Sato, Toyohiro Hirai","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the True Cardiovascular Risk in COPD: Is CACS-Tx the Right Approach?","authors":"Xiangxia Zeng","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ansa Cervicalis Stimulation During Non-REM Sleep in a Patient with Obstructive Sleep Apnea.","authors":"Yike Li, Alan R Schwartz, David Zealear, Megan E Hall, Matthew S Shotwell, Christopher J Lindsell, Silvana Bellotto, Katherine E Estes, Carol LeeAnn Wells, David T Kent","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children ≥6 Years with Cystic Fibrosis and at Least One <i>F508del</i> Allele: A 192-Week, Phase 3, Open-Label Extension Study.","authors":"Claire Wainwright, Susanna A McColley, Paul McNally, Michael Powers, Felix Ratjen, Jonathan H Rayment, George Retsch-Bogart, Erica Roesch, Bonnie Ramsey, Edward F McKone, Elizabeth Tullis, Marcus A Mall, Jennifer L Taylor-Cousar, David Waltz, Neil Ahluwalia, Chenghao Chu, Christina V Scirica, Jane C Davies","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children 6 through 11 years of age with cystic fibrosis (CF) and at least one <i>F508del</i> allele in a 24-week phase 3 study. Children completing this study could enroll into a 192-week extension study.</p><p><strong>Objectives: </strong>Evaluate long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years.</p><p><strong>Methods: </strong>In this 2-part (Part A [96-weeks] and Part B [96-weeks]) phase 3 extension study, children <12 years weighing <30 kg received ELX 100 mg once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and children weighing ≥ 30 kg or aged ≥12 years received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h.</p><p><strong>Measurements and main results: </strong>Sixty-four children (<i>F</i>/MF [n=36] and <i>F/F</i> [n=28]) received ≥ 1 dose of ELX/TEZ/IVA. Mean exposure was 156.2 weeks and 60.9% of children (n=39) completed treatment in both parts of this 192-week study. The primary endpoint was safety. All children had adverse events (AEs), which for most were mild (31.3%) or moderate (64.1%) and generally consistent with common manifestations of CF. Two children (3.1%) had non-serious AEs that lead to treatment discontinuation (increased alanine aminotransferase [n=1] and aggression [n=1]). Secondary endpoints focused on efficacy. From parent study baseline, improvements were seen in ppFEV₁ (9.6 percentage points; 95% CI: 5.4, 13.7), sweat chloride concentration (-57.9 mmol/L; 95% CI: -63.3, -52.5), CFQ-R respiratory domain score (10.0 points; 95% CI: 6.9, 13.0), LCI_2.5 (-2.33; 95% CI: -2.87, -1.79), and BMI z-score (0.39; 95% CI: 0.19, 0.59) at Week 192. Rate of pulmonary exacerbations per year was 0.05. The annualized rate of change in ppFEV₁ and LCI_2.5 was -0.09 percentage points (95% CI: -1.01, 0.84) and -0.07 units (95%CI: -0.12, -0.01), respectively.</p><p><strong>Conclusions: </strong>In this 4-year extension study in children ≥6 years, the longest clinical trial experience with a CFTR modulator in this pediatric population, ELX/TEZ/IVA remained generally safe and well-tolerated with no new safety findings. Clinically meaningful improvements in lung function, CFTR function, and nutritional status reported in the parent study were maintained. These results confirm the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.</p><p><strong>Clinicaltrials: </strong>gov, ID: NCT04183790.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}